发现致癌驱动基因突变使得针对性有效的靶向治疗个体化非小细胞肺癌（NSCLC）的转移治疗格局，然而，在可切除的NSCLC中实施新疗法受制于需要全生存率（OS）的长期随访。直到最近，早期可切除NSCLC患者的治疗一直局限于围手术期化疗，该治疗提供了一定的益处。然而，两种OS的替代终点获得了监管机构的认可，这使得新的治疗选择如辅助用奥西美替尼和阿特伊鲁鲁单抗得到了批准，从而为患者提供了改善疗效的新的治疗选择。在Ⅲ期肿瘤学试验中，OS曾被视为金标准的疗效指标，但是疾病无限期生存和无事件生存（EFS）现在已成为临床试验中OS的验证替代终点指标，在成熟的OS数据不可用时应加以考虑。在辅助NSCLC治疗中，另一个潜在的替代终点是基于循环肿瘤DNA（ctDNA）的微小残留病（MRD），但是需要进行前瞻性验证。对于新辅助靶向治疗快速发展的领域，EFS、重要的病理学反应和基于ctDNA的MRD是潜在替代终点。为了充分将转移性设置中个性化治疗的成功扩展到早期疾病，需要对这些潜在替代终点进行前瞻性验证研究，以加速药物疗效的评估。为了完成对替代终点数据的大规模验证，需要所有临床和监管各方的合作努力。本文讨论了肿瘤学试验中使用的替代终点的趋势，重点讨论了在早期可切除的EGFR突变NSCLC中选择适当主要终点的考虑。这是一个未满足需要新型治疗选择的领域。Copyright © 2023 The Authors. Elsevier B.V. 版权所有。

While the discovery of oncogenic driver mutations has personalized the metastatic non-small cell lung cancer (NSCLC) treatment landscape with effective targeted therapies, implementation of new treatments in resectable NSCLC has been limited due to the long follow-up needed for overall survival (OS). Until recently, treatment for patients with early-stage resectable NSCLC has been limited to perioperative chemotherapy, which provides modest benefits. However, the regulatory acceptance of two surrogate endpoints for OS has allowed recent approval of both adjuvant osimertinib and atezolizumab, providing patients with new treatment options to improve outcomes. In phase 3 oncology trials, OS has historically been viewed as the gold-standard efficacy measure, but disease-free survival and event-free survival (EFS) are now validated surrogate endpoints for OS in clinical trials and should be considered when mature OS data is unavailable. Another potential surrogate endpoint in the adjuvant NSCLC setting is circulating tumor DNA (ctDNA)-based minimal residual disease (MRD), although prospective validation is needed. For neoadjuvant targeted therapies, EFS, major pathologic response and ctDNA-based MRD are potential surrogate endpoints. To fully translate the success of the personalized treatment advances in the metastatic setting to earlier-stage disease, prospective validation studies of these potential surrogate endpoints that can accelerate the evaluation of drug efficacy are needed. A collaborative effort is also needed from all clinical and regulatory parties to collate surrogate endpoint data for large-scale validation. In this review we discuss the trends in surrogate endpoints used in oncology trials, with a focus on considerations for selecting appropriate primary endpoints in early-stage resectable EGFR-mutant NSCLC, an area of unmet need for novel treatment options.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.